Genetic Analysis of a Cohort of 275 Patients with Hyper-IgE Syndromes and/or Chronic Mucocutaneous Candidiasis
| Autor: | Peter Lunt, Mary Buchta, Laura Gámez-Díaz, Roya Sherkat, Pere Soler-Palacín, Desa Lilic, Christoph Klein, Turkan Patiroglu, Fulya Bektas Kut, Natalie Frede, Sara Sebnem Kilic, Katrin Hübscher, T. Prescott Atkinson, Jessica Rojas-Restrepo, Zahra Chavoshzadeh, Zineb Jouhadi, Ekrem Unal, Ömür Ardenyz, Moudjahed Saleh Al-Ddafari, Bodo Grimbacher, Niten Makwana, Fatih Celmeli, Nermeen Galal, Horst von Bernuth, Mehdi Adeli, Rainer Doffinger, Ilija Kirovski, Anne-Sophie Korganow, Margo L. Whiteford, Ayşe Akman Karakaş, Michele Proietti, Shiva Saghafi, V. Wahn, Andrés Caballero Garcia de Oteyza, Helen Rees, Robin Kobbe, Tuba Turul Özgür, Ana Berta Sousa, Juan Carlos Aldave-Becerra, Ayse Metin, Suranjith L. Seneviratne |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Eczema Cohort Studies Chronic mucocutaneous candidiasis Medical microbiology Extended Clinical Phenotype Immunology and Allergy Eosinophilia Sciences du Vivant [q-bio]/Immunologie Child Targeted panel sequencing Primary immunodeficiency Aire Gene Candidiasis Chronic Mucocutaneous Middle Aged Hyper-IgE syndrome Key Findings Job Syndrome Child Preschool Cohort Of-Function Mutations Deficiency Original Article Female medicine.symptom Dock8 Adult medicine.medical_specialty Adolescent Combined Immunodeficiency Immunology Infections Homozygous Mutations Young Adult medicine Genetics Humans business.industry Infant Stat1 Mutations Immunoglobulin E medicine.disease Dermatology Pneumonia Mutation Next-generation sequencing Impair business |
| Zdroj: | Journal of Clinical Immunology |
| Popis: | Hyper-IgE syndromes and chronic mucocutaneous candidiasis constitute rare primary immunodeficiency syndromes with an overlapping clinical phenotype. In recent years, a growing number of underlying genetic defects have been identified. To characterize the underlying genetic defects in a large international cohort of 275 patients, of whom 211 had been clinically diagnosed with hyper-IgE syndrome and 64 with chronic mucocutaneous candidiasis, targeted panel sequencing was performed, relying on Agilent HaloPlex and Illumina MiSeq technologies. The targeted panel sequencing approach allowed us to identify 87 (32 novel and 55 previously described) mutations in 78 patients, which generated a diagnostic success rate of 28.4%. Specifically, mutations in DOCK8 (26 patients), STAT3 (21), STAT1 (15), CARD9 (6), AIRE (3), IL17RA (2), SPINK5 (3), ZNF341 (2), CARMIL2/RLTPR (1), IL12RB1 (1), and WAS (1) have been detected. The most common clinical findings in this cohort were elevated IgE (81.5%), eczema (71.7%), and eosinophilia (62.9%). Regarding infections, 54.7% of patients had a history of radiologically proven pneumonia, and 28.3% have had other serious infections. History of fungal infection was noted in 53% of cases and skin abscesses in 52.9%. Skeletal or dental abnormalities were observed in 46.2% of patients with a characteristic face being the most commonly reported feature (23.1%), followed by retained primary teeth in 18.9% of patients. Targeted panel sequencing provides a cost-effective first-line genetic screening method which allows for the identification of mutations also in patients with atypical clinical presentations and should be routinely implemented in referral centers. Projekt DEAL; German Ministry of Education and Research (BMBF) [01E01303, 01ZX1306F, 01ZX1306A]; E-rare program of the European Commission EURO-CMC [01GM1502]; German Center for Infection Research DZIF [8000805-3, TTU-IICH_07.801]; German Research Foundation (DFG) [390939984, 39087428] Open Access funding enabled and organized by Projekt DEAL. Financial support for this research came from the German Ministry of Education and Research (BMBF, grant no. 01E01303; sys-INFLAME grant nos. 01ZX1306F and 01ZX1306A), from the E-rare program of the European Commission EURO-CMC (01GM1502), and from the German Center for Infection Research DZIF (8000805-3 and TTU-IICH_07.801). This study was supported by the German Research Foundation (DFG) under Germany's Excellence Strategy CIBSS (EXC-2189) (Project ID 390939984) and RESIST (EXC 2155) (Project ID 39087428). |
| Databáze: | OpenAIRE |
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